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Hyperinsulinemic hypoglycemia, familial, 8(HHF8)

MedGen UID:
1824072
Concept ID:
C5774299
Disease or Syndrome
Synonym: HHF8
 
Gene (location): SLC25A36 (3q23)
 
Monarch Initiative: MONDO:0859362
OMIM®: 620211

Definition

Familial hyperinsulinemic hypoglycemia-8 (HHF8) is an autosomal recessive disorder characterized by protein-related hypoglycemia and persistent mild hyperammonemia (summary by Shahroor et al., 2022). For a phenotypic description and a discussion of genetic heterogeneity of familial hyperinsulinemic hypoglycemia, see HHF1 (256450). [from OMIM]

Clinical features

From HPO
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Chronic constipation
MedGen UID:
98325
Concept ID:
C0401149
Sign or Symptom
Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Expressive language delay
MedGen UID:
141568
Concept ID:
C0454641
Disease or Syndrome
A delay in the acquisition of the ability to use language to communicate needs, wishes, or thoughts.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hypoglycemic seizures
MedGen UID:
164079
Concept ID:
C0877056
Disease or Syndrome
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
Hypercholesterolemia
MedGen UID:
5687
Concept ID:
C0020443
Disease or Syndrome
An increased concentration of cholesterol in the blood.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Increased C-peptide level
MedGen UID:
894029
Concept ID:
C4280763
Finding
An elevated concentration of C-peptide in the circulation. Since C-peptide is secreted in equimolar amounts to insulin, this feature correlates with increased insulin secretion.
Hyperammonemia
MedGen UID:
1802066
Concept ID:
C5574662
Laboratory or Test Result
An increased concentration of ammonia in the blood.
Hyperinsulinemia
MedGen UID:
43779
Concept ID:
C0020459
Disease or Syndrome
An increased concentration of insulin in the blood.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Elevated circulating thyroid-stimulating hormone concentration
MedGen UID:
108325
Concept ID:
C0586553
Finding
Increased concentration of thyroid-stimulating hormone (TSH) in the blood circulation.

Recent clinical studies

Etiology

Sivasubramanian M, Avari P, Gilbert C, Doodson L, Morgan K, Oliver N, Shah P
Front Endocrinol (Lausanne) 2023;14:1265076. Epub 2023 Sep 26 doi: 10.3389/fendo.2023.1265076. PMID: 37822600Free PMC Article
Li M, Gong S, Han X, Zhang S, Ren Q, Cai X, Luo Y, Zhou L, Zhang R, Liu W, Zhu Y, Zhou X, Sun Y, Li Y, Ma Y, Ji L
J Diabetes 2021 Jul;13(7):542-553. Epub 2021 Jan 4 doi: 10.1111/1753-0407.13144. PMID: 33300273
Louvigne M, Rouleau S, Caldagues E, Souto I, Montcho Y, Bouvagnet AM, Baud O, Carel JC, Gascoin G, Coutant R
PLoS One 2018;13(5):e0195383. Epub 2018 May 3 doi: 10.1371/journal.pone.0195383. PMID: 29723237Free PMC Article
Ismail D, Smith VV, de Lonlay P, Ribeiro MJ, Rahier J, Blankenstein O, Flanagan SE, Bellanné-Chantelot C, Verkarre V, Aigrain Y, Pierro A, Ellard S, Hussain K
J Clin Endocrinol Metab 2011 Jan;96(1):24-8. Epub 2010 Oct 13 doi: 10.1210/jc.2010-1524. PMID: 20943779Free PMC Article
al-Rabeeah A, al-Ashwal A, al-Herbish A, al-Jurayyan N, Sakati N, Abobakr A
J Pediatr Surg 1995 Aug;30(8):1119-21. doi: 10.1016/0022-3468(95)90001-2. PMID: 7472962

Diagnosis

Sivasubramanian M, Avari P, Gilbert C, Doodson L, Morgan K, Oliver N, Shah P
Front Endocrinol (Lausanne) 2023;14:1265076. Epub 2023 Sep 26 doi: 10.3389/fendo.2023.1265076. PMID: 37822600Free PMC Article
Li M, Gong S, Han X, Zhang S, Ren Q, Cai X, Luo Y, Zhou L, Zhang R, Liu W, Zhu Y, Zhou X, Sun Y, Li Y, Ma Y, Ji L
J Diabetes 2021 Jul;13(7):542-553. Epub 2021 Jan 4 doi: 10.1111/1753-0407.13144. PMID: 33300273
Sethi A, Foulds N, Ehtisham S, Ahmed SH, Houghton J, Colclough K, Didi M, Flanagan SE, Senniappan S
J Clin Res Pediatr Endocrinol 2020 Nov 25;12(4):420-426. Epub 2020 Jan 28 doi: 10.4274/jcrpe.galenos.2019.2019.0106. PMID: 31989990Free PMC Article
Louvigne M, Rouleau S, Caldagues E, Souto I, Montcho Y, Bouvagnet AM, Baud O, Carel JC, Gascoin G, Coutant R
PLoS One 2018;13(5):e0195383. Epub 2018 May 3 doi: 10.1371/journal.pone.0195383. PMID: 29723237Free PMC Article
al-Rabeeah A, al-Ashwal A, al-Herbish A, al-Jurayyan N, Sakati N, Abobakr A
J Pediatr Surg 1995 Aug;30(8):1119-21. doi: 10.1016/0022-3468(95)90001-2. PMID: 7472962

Therapy

Clemente M, Cobo P, Antolín M, Campos A, Yeste D, Tomasini R, Caimari M, Masas M, García-Arumí E, Fernández-Cancio M, Baz-Redón N, Camats-Tarruella N
J Clin Endocrinol Metab 2023 Oct 18;108(11):e1316-e1328. doi: 10.1210/clinem/dgad280. PMID: 37216904
Perge K, Nicolino M
Rev Endocr Metab Disord 2022 Oct;23(5):1063-1078. Epub 2022 Aug 23 doi: 10.1007/s11154-022-09749-2. PMID: 35996042
Skajaa GO, Mathiesen ER, Iyore E, Beck-Nielsen H, Jimenez-Solem E, Damm P
BMC Res Notes 2014 Nov 17;7:804. doi: 10.1186/1756-0500-7-804. PMID: 25404386Free PMC Article
Flanagan SE, Kapoor RR, Mali G, Cody D, Murphy N, Schwahn B, Siahanidou T, Banerjee I, Akcay T, Rubio-Cabezas O, Shield JP, Hussain K, Ellard S
Eur J Endocrinol 2010 May;162(5):987-92. Epub 2010 Feb 17 doi: 10.1530/EJE-09-0861. PMID: 20164212Free PMC Article
al-Rabeeah A, al-Ashwal A, al-Herbish A, al-Jurayyan N, Sakati N, Abobakr A
J Pediatr Surg 1995 Aug;30(8):1119-21. doi: 10.1016/0022-3468(95)90001-2. PMID: 7472962

Prognosis

Li M, Gong S, Han X, Zhang S, Ren Q, Cai X, Luo Y, Zhou L, Zhang R, Liu W, Zhu Y, Zhou X, Sun Y, Li Y, Ma Y, Ji L
J Diabetes 2021 Jul;13(7):542-553. Epub 2021 Jan 4 doi: 10.1111/1753-0407.13144. PMID: 33300273
Sethi A, Foulds N, Ehtisham S, Ahmed SH, Houghton J, Colclough K, Didi M, Flanagan SE, Senniappan S
J Clin Res Pediatr Endocrinol 2020 Nov 25;12(4):420-426. Epub 2020 Jan 28 doi: 10.4274/jcrpe.galenos.2019.2019.0106. PMID: 31989990Free PMC Article
Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, Shield JP, Ellard S, Ferrer J, Hattersley AT
PLoS Med 2007 Apr;4(4):e118. doi: 10.1371/journal.pmed.0040118. PMID: 17407387Free PMC Article
Desai MP, Khatri JV
Indian Pediatr 1998 Apr;35(4):317-28. PMID: 9770886
al-Rabeeah A, al-Ashwal A, al-Herbish A, al-Jurayyan N, Sakati N, Abobakr A
J Pediatr Surg 1995 Aug;30(8):1119-21. doi: 10.1016/0022-3468(95)90001-2. PMID: 7472962

Clinical prediction guides

Clemente M, Cobo P, Antolín M, Campos A, Yeste D, Tomasini R, Caimari M, Masas M, García-Arumí E, Fernández-Cancio M, Baz-Redón N, Camats-Tarruella N
J Clin Endocrinol Metab 2023 Oct 18;108(11):e1316-e1328. doi: 10.1210/clinem/dgad280. PMID: 37216904
Li M, Gong S, Han X, Zhang S, Ren Q, Cai X, Luo Y, Zhou L, Zhang R, Liu W, Zhu Y, Zhou X, Sun Y, Li Y, Ma Y, Ji L
J Diabetes 2021 Jul;13(7):542-553. Epub 2021 Jan 4 doi: 10.1111/1753-0407.13144. PMID: 33300273
Louvigne M, Rouleau S, Caldagues E, Souto I, Montcho Y, Bouvagnet AM, Baud O, Carel JC, Gascoin G, Coutant R
PLoS One 2018;13(5):e0195383. Epub 2018 May 3 doi: 10.1371/journal.pone.0195383. PMID: 29723237Free PMC Article
Cabezas OR, Flanagan SE, Stanescu H, García-Martínez E, Caswell R, Lango-Allen H, Antón-Gamero M, Argente J, Bussell AM, Brandli A, Cheshire C, Crowne E, Dumitriu S, Drynda R, Hamilton-Shield JP, Hayes W, Hofherr A, Iancu D, Issler N, Jefferies C, Jones P, Johnson M, Kesselheim A, Klootwijk E, Koettgen M, Lewis W, Martos JM, Mozere M, Norman J, Patel V, Parrish A, Pérez-Cerdá C, Pozo J, Rahman SA, Sebire N, Tekman M, Turnpenny PD, Hoff WV, Viering DHHM, Weedon MN, Wilson P, Guay-Woodford L, Kleta R, Hussain K, Ellard S, Bockenhauer D
J Am Soc Nephrol 2017 Aug;28(8):2529-2539. Epub 2017 Apr 3 doi: 10.1681/ASN.2016121312. PMID: 28373276Free PMC Article
Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, Shield JP, Ellard S, Ferrer J, Hattersley AT
PLoS Med 2007 Apr;4(4):e118. doi: 10.1371/journal.pmed.0040118. PMID: 17407387Free PMC Article

Recent systematic reviews

Perge K, Nicolino M
Rev Endocr Metab Disord 2022 Oct;23(5):1063-1078. Epub 2022 Aug 23 doi: 10.1007/s11154-022-09749-2. PMID: 35996042

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