A Hong Kong Chinese kindred with familial hypocalciuric hypercalcaemia caused by AP2S1 mutation

Familial hypocalciuric hypercalcaemia (FHH) is a genetic disorder of altered calcium homeostasis. Mutations in the CASR, GNA11 and AP2S1 genes have been reported to cause FHH. We report a Hong Kong Chinese kindred with FHH type 3 (FHH3) caused by mutations in AP2S1. The proband, a 51-year-old woman with hypercalcaemia, was initially diagnosed to have primary hyperparathyroidism but repeated parathyroidectomy failed to normalize her plasma calcium concentrations. Later, FHH was suspected and yet no mutations were identified in the CASR gene which causes FHH type 1 (FHH1), the most common form of FHH. Genetic testing of AP2S1 revealed a heterozygous c.43C>T (p.Arg15Cys) mutation, confirming the diagnosis of FHH3. The elder brother and niece of the proband, who both have hypercalcaemia, were found to harbour the same mutation. To our knowledge, this is the first Chinese kindred of FHH3 reported in the English literature.

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Clinical Presentation and Management Approach in a Case of Familial Hypocalciuric Hypercalcemia Type 3 Due to APS21 Gene Mutation

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.381 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A188-A188

Author(s):

Sahar A Elsheikh ◽

Henry M Blunk ◽

Scott Wilhelm

Keyword(s):

Case Report ◽

Genetic Testing ◽

Primary Hyperparathyroidism ◽

Calcium Homeostasis ◽

Clinical Presentation ◽

Genetic Disorder ◽

Management Approach ◽

Familial Hypocalciuric Hypercalcemia ◽

Surgical Options ◽

Type 3

Abstract Familial hypocalciuric hypercalcemia (FHH) is a genetic disorder caused by dysfunctional calcium homeostasis. Thus far, three types of FHH are known to be caused by mutations inCASR (FHH1), GNA11 (FHH2), and AP2S1 (FHH3). The patient in this case report is a 36-year old male that initially presented for a second opinion after being diagnosed with Primary Hyperparathyroidism(PHPT) with subsequent parathyroidectomy done at another institute, and developed recurrent symptomatic hypercalcemia. Prior to considering this patient for further surgical options, he underwent genetic testing, which revealed he had c.43C>T (p.Arg15Cys) mutation in the AP2S1 gene diagnostic of Familial Hypocalciuric Hypercalcemia Type 3 (FHH3). The patient’s father and sister also have hypercalcemia, and have been offered genetic testing. There have been cases reported of patients with FHH3 that have symptomatic hypercalcemia and that have associated cognitive issues. Many patients with FHH can be misdiagnosed and may undergo unnecessary parathyroidectomy. This case report further elucidates the need to raise awareness of FHH.

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Gaucher's Disease - A case report

MVP Journal of Medical Sciences ◽

10.18311/mvpjms/2015/v2/i2/788 ◽

2015 ◽

Vol 2 (2) ◽

pp. 130

Author(s):

Preeti Bajaj ◽

Jyoti Kasture ◽

Balbir Singh Shah

Keyword(s):

Autosomal Recessive ◽

Genetic Disorder ◽

Early Adulthood ◽

Lysosomal Storage ◽

Gaucher's Disease ◽

Gaucher’S Disease ◽

Type 3 ◽

Storage Disorders

Gaucher's Disease (GD) is an autosomal recessive systemic lysosomal storage disorder which is characterized by glucocerebroside deposition in cells of the macrophage-monocyte system as a result of a deficiency in lysosomal P-glycosidase (glucocerebrosidase). GD is a rare genetic disorder. It is the most common amongst the lysosomal storage disorders. GD has been categorised into three types based on the presence of central nervous involvement1. Type 1 is a non-neuronopathic form that presents in childhood or early adulthood. Type 2 is acute neuronopathic form that presents in childhood. It progresses rapidly and is fatal. Type 3 is chronic non-neuronopathic form that presents in childhood but is slowly progressive. Here we describe a case of a three and a half year old male child in whom a diagnosis of Gaucher's disease was made based on bone marrow biopsy and later confirmed by glucocerebrosidase levels estimation.

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Failure of Cimetidine to Affect Calcium Homeostasis in Familial Primary Hyperparathyroidism (Multiple Endocrine Neoplasia, Type 1)*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem-51-4-912 ◽

1980 ◽

Vol 51 (4) ◽

pp. 912-914 ◽

Cited By ~ 14

Author(s):

MICHAEL F. ROBINSON ◽

ALVIN B. HAYLES ◽

HUNTER HEATH

Keyword(s):

Primary Hyperparathyroidism ◽

Calcium Homeostasis ◽

Multiple Endocrine Neoplasia ◽

Multiple Endocrine Neoplasia Type ◽

Endocrine Neoplasia ◽

Endocrine Neoplasia Type ◽

Familial Primary Hyperparathyroidism

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Metreleptin as A Rescue Therapy in A Patient With A Novel Mutation for Familial Partial Lipodystrophy Type 3, Originally Presenting as Type 1 Diabetes.

10.21203/rs.3.rs-154503/v1 ◽

2021 ◽

Author(s):

VAIA LAMBADIARI ◽

AIKATERINI KOUNTOURI ◽

EIRINI MARATOU ◽

STAVROS LIATIS ◽

GEORGE DIMITRIADIS ◽

...

Keyword(s):

Type 1 Diabetes ◽

Effective Treatment ◽

Novel Mutation ◽

Genetic Disorder ◽

Synthetic Analogue ◽

Metabolic Complications ◽

Partial Lipodystrophy ◽

Familial Partial Lipodystrophy ◽

Type 3

Abstract Background: Familial partial lipodystrophy type 3 (FPLD3) is a very rare autosomal dominant genetic disorder which is caused by mutations in the peroxisome proliferator activated receptor gamma (PPARG) gene. It is characterized by a partial loss of adipose tissue leading to subnormal leptin secretion and metabolic complications. Metreleptin, a synthetic analogue of human leptin, is an effective treatment for generalized lipodystrophies, but the evidence for efficacy in patients with FPLD3 is scarce. Case presentation: We present a 61-year-old woman, initially misdiagnosed as type 1 diabetes since the age of 29, with severe insulin resistance, who gradually displayed a more generalized form of lipoatrophy and extreme hypertriglyceridemia, hypertension and multiple manifestations of cardiovascular disease. She was found to carry a novel mutation leading to PPARGGlu157Gly variant. After six months of metreleptin treatment HbA1c decreased from 10% to 7.9% and fasting plasma triglycerides were dramatically reduced from 2.919 mg/dl to 198 mg/dl. Conclusions: This case highlights the importance of early recognition of FPLD syndromes otherwise frequently observed as a difficult-to-classify and manage diabetes cases, in order to prevent cardiovascular complications. Metreleptin may be an effective treatment for FPLD3.

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