Chinese Medical Journal 2003;116(12):1952-1954
Pearson’s syndrome: a rare cause of non-immune hydrops fetalis

LI Chak Ho 李澤荷,  LAM Ching Wan 林青雲,  LEE Chi Wai Anselm 李志偉,  KWONG Ngai Shan 鄺毅山,  SZETO Siu Cheong 司徒紹昌

LI Chak Ho 李澤荷 (Department of Paediatrics ,Tuen Mun Hospital, New Territories, Hong Kong, China)

LAM Ching Wan 林青雲 (Department of Chemical Pathology, the Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong, China)

LEE Chi Wai Anselm 李志偉 (Department of Paediatrics ,Tuen Mun Hospital, New Territories, Hong Kong, China)

KWONG Ngai Shan 鄺毅山 (Department of Paediatrics ,Tuen Mun Hospital, New Territories, Hong Kong, China)

SZETO Siu Cheong 司徒紹昌 (Department of Pathology, Tuen Mun Hospital, New Territories, Hong Kong, China)

Correspondence to:C.H. Li,Department of Paediatrics, Tuen Mun Hospital, New Territories, Hong Kong, China (Tel: 852-2468-5111. Fax:852-2456-9111. E-mail:drchli@hotmail.com)
Keywords
hydrops fetalis ; mitochondrial cytopathy ; Pearson’s syndrome; sideroblastic anaemia
Abstract

Pearson’s syndrome, or Pearson’s marrow-pancreas syndrome, was first described in 1979 in four unrelated children.[1] It is characterized by refractory sideroblastic anaemia with vacuolization of marrow progenitor cells, and exocrine pancreatic dysfunction. Its progressive nature, multisystem involvement and metabolic disturbances led to the subsequent identification of a unique mitochondrial DNA deletion in most affected patients.[2] Despite the relentless clinical course, the majority of the patients with Pearson’s syndrome present insidiously. Life-threatening presentation at birth is extremely rare. We report a case of Pearson’s syndrome presenting with severe hydrops fetalis.

CASE REPORT

A Chinese girl was born to a pair of healthy non-consanguineous parents. Mother had given birth to a healthy boy previously. The pregnancy was uneventful till 38 weeks of gestation when antepartum haemorrhage occurred. On ultrasound examination, placenta previa and a hydropic fetus were found. The baby was delivered by emergency Caesarian section with a birth weight of 2.855 kg. She was pale and grossly edematous with cardiomegaly, pleural effusion, hepatosplenomegaly and massive ascites. The first haemoglobin was 2.5 g/dl with a reticulocyte count of 0.3%. The total leukocyte, neutrophil, and platelet counts were 10.6×109/L, 2.4×10(9)/L and 76×109/L, respectively. The child was immediately treated with mechanical ventilation, circulatory support and a double volume exchange transfusion. On day 3 of life, the anaemia was corrected, and the child’s condition was stable without cardio-pulmonary support.

Investigations for haemolysis, haemoglobinopathy, and congenital cytomegalovirus or parvovirus infection were negative. The karyotype and clastrogenic test with diepoxybutane for Fanconi’s anaemia were normal. A bone marrow aspirate yielded aparticular smear, but the trephine biopsy showed normal haemopoiesis without abnormal infiltrates. Examination of the parents’ blood did not show any features of anaemia or haemo-globinopathy. The Kleihauer’s test for fetomaternal transfusion was negative.

The subsequent neonatal course was largely uneventful except for persistent neutropenia (0.4×109/L-0.7×109/L), thrombocytopenia (30×109/L-60×109/L) and a progressive drop in haemoglobin. Repeated transfusions were needed monthly when the haemoglobin dropped to less than 7.0 g/dl. However, the child thrived and developed normally. There was no diarrhoea or metabolic acidosis.

At 3 months of age, a repeat bone marrow examination was performed. Haemopoiesis remained active. A small proportion of myeloid and erythroid precursors showed vacuolization ( Fig. ) and ringed sideroblasts were seen on the iron stain. The features were most consistent with a diagnosis of Pearson’s syndrome, which was confirmed by genetic analysis of the mitochondrial genome. A 4977-bp deletion was detected in the patient’s mitochondrial DNA from the bone marrow cells by polymerase chain reaction and direct DNA sequencing as described by McShane et al.[3] Study on the peripheral blood obtained from both parents and the elder brother were negative for the deletion.

With the diagnosis in mind, we continued the transfusion therapy only when her haemoglobin dropped below 7.0 g/dl. Improvement in the platelet and neutrophil counts was seen after the first and the second month of life, respectively. Anaemia improved after 7 months of life and the last transfusion was given at 9 months of age. At 15 months old, the girl had normal haemoglobin and white cell counts, with a mild thrombocytopenia of 133×109/L.

DISCUSSION

Since the first description of Pearson’s syndrome in 1979,[1] more than 40 cases have been reported.[4] The condition can now be reliably identified by the presence of a deletion of the mitochondrial DNA involving enzymes of oxidative phosphorylation, with a 4977-bp deletion found in the majority of patients studied.[2] As one of the mitochondrial cytopathy syndromes, multisystemic involvement is recognized with refractory sideroblastic anaemia, variable pancytopenia, exocrine and endocrine pancreatic insufficiency, metabolic acidosis, failure to thrive, and hypoparathyrodism.[5] A susceptibility to infectious complications has also been described.[6] Some of the clinical features overlap with Kearns-Sayre syndrome, and progression into Kearns-Sayre syndrome has been reported.[7] No effective treatment is available.

Haematological manifestation remains the most classical features of Pearson’s syndrome.[1] The onset is usually insidious with anaemia diagnosed before one month of age in 25% and by 6 months in 70% of affected infants.[4] Life-threatening presentation with hydrops fetalis is extremely rare with only two cases reported previously.[8,9] Rotig et al[8] first described the occurrence in a full term newborn and Oblender et al[9] reported another case in a premature infant. Similar to our patient, both reported cases were salvaged with exchange transfusion. However, the first patient developed complications at 8 months of age and died at 25 months from hepatic failure. The clinical course of the second patient was not mentioned. With less than a handful of cases, it is difficult to predict if such an early presentation would portend a better or poorer prognosis. Despite the drastic neonatal course, the subsequent spontaneous amelioration of the cytopenia in our case supports the previous notion that aggressive treatment such as bone marrow transplantation is often unnecessary.

The recognition of Pearson’s syndrome in the newborn and differentiation from other bone marrow failure syndromes can be difficult. In particular, congenital sideroblastic anaemia shares with Pearson’s syndrome the clinical features of refractory anaemia and the presence of ringed sideroblasts in the bone marrow. However, congenital sideroblastic anaemia is usually an X-linked recessive disease. The affected individual is typically a male patient, and treatment with pyridoxine may be effective. Indeed, the female patient reported by Andersen et al[10] who also presented with hydrops foetalis, refractory anaemia, recurrent diarrhoea and early death might well be a case of Pearson’s syndrome should molecular study for mitochondrial DNA deletion have been carried out. Bone marrow trephine biopsy cannot substitute for marrow aspiration cytology as illustrated in our patient, because the characteristic cytoplasmic vacuolization is lost after fixation. Hence, the diagnosis of Pearson’s syndrome can be missed unless specific features in the bone marrow and mitochondrial DNA deletion are looked for. With the decreasing incidence of hydrops foetalis secondary to haemolytic disorders as a result of improved antenatal diagnosis,[11] we suggest that Pearson’s syndrome should be actively searched for every case of hydrops foetalis associated with severe anaemia.


Acknowledgement: We would like to thank Mr. Kent Tsang from the Department of Pathology, Prince of Wales Hospital, Hong Kong, China, for his technical assistance in the marrow progenitor cell culture.

REFERENCES

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