Non-classical 11β-hydroxylase deficiency caused by compound heterozygous mutations: a case study and literature review

Objective: Hypophosphatemic rickets with hypercalciuria (HHRH) is a rare, recessively-inherited form of rickets caused by homozygous or compound heterozygous mutations in the SLC34A3 gene that encodes the renal tubular phosphate transporter protein NaPi2c. The bone phenotype varies from severe rickets to no disease. Accurate diagnosis is important as the treatment differs from other forms of rickets. Methods: The patient was a 12-year-old boy from the Indian subcontinent with florid hypophosphatemic rickets. A targeted gene panel to search for mutations in genes associated with inherited forms of rickets was performed. We also completed a literature search of published cases of HHRH. Results: The targeted gene panel demonstrated a novel homozygous SLC34A3 mutation: c.1339 G>A (p.Ala447Thr). His parents were heterozygous for the mutation. In our literature review we found that people with homozygous SLC34A3 mutations were more likely to have rickets than those with compound heterozygous mutations (85% versus 45%, p<0.002) and that serum phosphate z scores were lower in those with rickets than those without (−3.3 with a standard deviation of 1.5 versus −2.1 with a standard deviation of 1.5, p<0.005). Conclusion: The bone phenotype of HHRH is related to the nature of the mutation and serum phosphate levels. Targeted gene panels can aid in the accurate diagnosis of inherited forms of rickets, and facilitate correct treatment.

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A Chinese newborn with Zellweger syndrome and compound heterozygous mutations novel in the PEX1 gene: a case report and literature review

Translational Pediatrics ◽

10.21037/tp-20-167 ◽

2021 ◽

Vol 10 (2) ◽

pp. 446-453

Author(s):

Pei Lu ◽

Li Ma ◽

Jingjing Sun ◽

Xiaohui Gong ◽

Cheng Cai

Keyword(s):

Case Report ◽

Literature Review ◽

Zellweger Syndrome ◽

Compound Heterozygous ◽

Compound Heterozygous Mutations

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Renal hypouricemia caused by novel compound heterozygous mutations in the SLC22A12 gene: a case report with literature review

BMC Medical Genetics ◽

10.1186/s12881-018-0595-8 ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Zhaowei Zhou ◽

Lidan Ma ◽

Juan Zhou ◽

Zhijian Song ◽

Jinmai Zhang ◽

...

Keyword(s):

Case Report ◽

Literature Review ◽

Compound Heterozygous ◽

Renal Hypouricemia ◽

Compound Heterozygous Mutations

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Aldosterone signaling defect in young infants: single-center report and review

BMC Endocrine Disorders ◽

10.1186/s12902-021-00811-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Melati Wijaya ◽

Huamei Ma ◽

Jun Zhang ◽

Minlian Du ◽

Yanhong Li ◽

...

Keyword(s):

Clinical Picture ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Homozygous Mutation ◽

Hydroxylase Deficiency ◽

Salt Wasting ◽

Young Infants ◽

Adrenal Imaging ◽

Compound Heterozygous Mutations ◽

21 Hydroxylase Deficiency

Abstract Background Aldosterone (Ald) is a crucial factor in maintaining electrolyte and water homeostasis. Defect in either its synthesis or function causes salt wasting (SW) manifestation. This disease group is rare, while most reported cases are sporadic. This study aimed to obtain an overview of the etiology and clinical picture of patients with the above condition and report our rare cases. Methods A combination of retrospective review and case studies was conducted at the Pediatric Endocrine unit of The First Affiliated Hospital Sun Yat Sen University from September 1989 to June 2020. Results A total of 187 patients with SW were enrolled, of which 90.4% (n = 169) were diagnosed with congenital adrenal hyperplasia (CAH). SW type 21-hydroxylase deficiency accounted for 98.8% (n = 167) of CAH diagnosis, while 1.2% (n = 2) was of lipoid CAH. Non-CAH comprised 9.6% (n = 18) of the total patients whose etiologies included SF-1 gene mutation (n = 1), X-linked adrenal hypoplasia congenita (n = 9), aldosterone synthase deficiency (ASD, n = 4), and pseudo-hypoaldosteronism type 1 (PHA1, n = 1). Etiologies were not identified in three patients. All of patients with ASD and PHA1 exhibited SW syndrome in their early neonatal period. DNA sequencing showed mutations of CYP11B2 for P1-P4 and NR3C2 for P5. P1 and P2 were sibling brothers affected by compound heterozygous mutations of c.1121G > A (p.R374Q) and c.1486delC p.(L496fs); likewise, P4 was identified with compound heterozygous mutations of c.1200 + 1G > A and c.240–1 G > T; meanwhile P3 demonstrated c.1303G > A p.(G435S) homozygous mutation in CYP11B2 gene. Lastly, P5 showed c.1768 C > T p.(R590*) heterozygous mutation in the NR3C2 gene. Conclusion Etiology of infant with aldosterone defect was mostly congenital. Renal and adrenal imaging are recommended to exclude renal causes. If clinical picture is suggestive, normal plasma Ald in early infancy cannot rule out aldosterone insufficiency.

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