Diagnosis and Treatment > Signs and Symptoms
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Summary
Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare endocrine disorders characterised by normal renal function and renal resistance to the action of the parathyroid hormone. Type 1A (PHP1A), which is the most common variant, also include developmental and skeletal defects named as Albright hereditary osteodystrophy (AHO). We present two cases, a 54- and a 33-year-old male diagnosed with PHP who were referred to us for persistently high levels of serum calcitonin. AHO and multinodular goitre were present in the 54-year-old male, while the second patient was free of skeletal deformities and his thyroid gland was of normal size and without nodular appearance. We performed GNAS molecular analysis (methylation status and copy number analysis by MS-MLPA) in genomic DNA samples for both patients. The analysis revealed a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1, in the patient with the clinical diagnosis of PHP1A. This amino acid change appears to be in accordance with the clinical diagnosis of the patient. The genomic DNA analysis of the second patient revealed the presence of the recurrent 3-kb deletion affecting the imprinting control region localised in the STX16 region associated with the loss of methylation (LOM) at the GNAS A/B differentially methylated region and consistent with the diagnosis of an autosomal dominant form of PHP type 1B (PHP1B). In conclusion, hypercalcitoninaemia may be encountered in PHP1A and PHP1B even in the absence of thyroid pathology.
Learning points:
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We describe a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1 as the cause of PHP1A.
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Hypercalcitoninaemia in PHP1A is considered an associated resistance to calcitonin, as suggested by the generalised impairment of Gsα-mediated hormone signalling.
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GNAS methylation defects, as in type PHP1B, without thyroid pathology can also present with hypercalcitoninaemia.
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Summary
Hypokalaemia may present as muscle cramps and Cardiac arrhythmias. This is a condition commonly encountered by endocrinologists and general physicians alike. Herein, we report the case of a 43-year-old gentleman admitted with hypokalaemia, who following subsequent investigations was found to have Gitelman's syndrome (GS). This rare, inherited, autosomal recessive renal tubular disorder is associated with genetic mutations in the thiazide-sensitive sodium chloride co-transporter and magnesium channels in the distal convoluted tubule. Patients with GS typically presents at an older age, and a spectrum of clinical presentations exists, from being asymptomatic to predominant muscular symptoms. Clinical suspicion should be raised in those with hypokalaemic metabolic alkalosis associated with hypomagnesaemia. Treatment of GS consists of long-term potassium and magnesium salt replacement. In general, the long-term prognosis in terms of preserved renal function and life expectancy is excellent. Herein, we discuss the biochemical imbalance in the aetiology of GS, and the case report highlights the need for further investigations in patients with recurrent hypokalaemic episodes.
Learning points
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Recurrent hypokalaemia with no obvious cause warrants investigation for hereditary renal tubulopathies.
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GS is the most common inherited renal tubulopathy with a prevalence of 25 per million people.
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GS typically presents at an older age and clinical suspicion should be raised in those with hypokalaemic metabolic alkalosis associated with hypomagnesaemia.
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Confirmation of diagnosis is by molecular analysis for mutation in the SLC12A3 gene.
